Hydrochlorothiazide Tablets

This article is compiled based on the United States Pharmacopeia (USP) – 2025 Edition

Issued and maintained by the United States Pharmacopeial Convention (USP)

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DEFINITION 

Hydrochlorothiazide Tablets contain NLT 90.0% and NMT 110.0% of the labeled amount of hydrochlorothiazide (C₇H₈ClN₃O₄S₂)

1 IDENTIFICATION 

Infrared Absorption 

Sample: Transfer an amount, equivalent to 50 mg of hydrochlorothiazide from finely powdered Tablets, to a 50-mL volumetric flask. Add 20 mL of sodium hydroxide solution (1 in 125), and shake vigorously for 15 min. Dilute with the same solvent to volume, mix, and filter, discarding the first few mL of the filtrate. Transfer 5 mL of the filtrate to a 125-mL separator, and add 5 mL of hydrochloric acid (1 in 10). Extract with 50 mL of ether, pass the ether extract through a small, dry, folded filter paper, and evaporate to dryness. Add 5 mL of alcohol, and again evaporate to dryness. 

Acceptance criteria: The IR absorption spectrum of a potassium bromide dispersion of the residue obtained from the Sample exhibits maxima only at the same wavelengths as that of a similar preparation of USP Hydrochlorothiazide RS previously dissolved in alcohol and recovered by evaporating the solution to dryness. 

The retention time of the major peak of the Sample solution corresponds to that of the Standard solution, as obtained in the Assay. 

2 ASSAY 

Procedure 

Mobile phase: Acetonitrile and 0.1 M monobasic sodium phosphate (1:9). Adjust with phosphoric acid to a pH of 3.0 ± 0.1, and filter. System suitability solution: 0.15 mg/mL of chlorothiazide and 0.15 mg/mL of USP Hydrochlorothiazide RS in Mobile phase. [Note—A volume of acetonitrile not exceeding 10% of the total volume of solution may be used to dissolve the USP Reference Standard.] Standard solution: 0.15 mg/mL of USP Hydrochlorothiazide RS in Mobile phase 

Sample solution: Nominally 0.15 mg/mL of hydrochlorothiazide prepared as follows. Equivalent to 30 mg of hydrochlorothiazide from finely powdered Tablets (NLT 20) in a 200-mL volumetric flask. Add 20 mL of Mobile phase, sonicate for 5 min, and add 20 mL of acetonitrile. Sonicate for 5 min, add 50 mL of Mobile phase, and shake by mechanical means for 10 min. Dilute with Mobile phase to volume, mix, and filter, discarding the first 10 mL of the filtrate. 

Chromatographic system 

(See Chromatography 〈621〉, System Suitability.) 

Mode: LC 

Detector: UV 254 nm 

Column: 4.6-mm × 25-cm; packing L1 

Flow rate: 2 mL/min 

Injection volume: 20 µL 

System suitability 

Samples: System suitability solution and Standard solution 

[Note—The relative retention times for chlorothiazide and hydrochlorothiazide are about 0.8 and 1.0, respectively.] 

Suitability requirements 

Resolution: NLT 2.0 between chlorothiazide and hydrochlorothiazide, System suitability solution 

Relative standard deviation: NMT 1.5%, Standard solution 

Analysis 

Samples: Standard solution and Sample solution 

Calculate the percentage of the labeled amount of hydrochlorothiazide (C₇H₈ClN₃O₄S₂) in the portion of Tablets taken:  

Result = (r_U/r_S) × (C_S/C_U) × 100 

r_U = peak response of hydrochlorothiazide from the Sample solution  

r_S = peak response of hydrochlorothiazide from the Standard solution 

C_S = concentration of USP Hydrochlorothiazide RS in the Standard solution (µg/mL) 

C_U = nominal concentration of hydrochlorothiazide in the Sample solution (µg/mL) 

Acceptance criteria: 90.0%–110.0% 

3 PERFORMANCE TESTS 

Dissolution 〈711〉 

Medium: 0.1 N hydrochloric acid; 900 mL 

Apparatus 1: 100 rpm 

Time: 60 min 

Standard solution: USP Hydrochlorothiazide RS at a known concentration in Medium 

Sample solution: Pass a portion of solution under test through a suitable filter. Dilute with Medium as necessary in comparison with the Standard solution. 

Instrumental conditions 

(See Ultraviolet-Visible Spectroscopy 〈857〉.) 

Mode: UV 

Analytical wavelength: About 272 nm 

Analysis 

Samples: Standard solution and Sample solution 

Tolerances: NLT 60% (Q) of the labeled amount of hydrochlorothiazide (C₇H₈ClN₃O₄S₂) is dissolved. 

Uniformity of Dosage Units 〈905〉: Meet the requirements 

4 IMPURITIES 

Organic Impurities 

Mobile phase, System suitability solution, Sample solution, Chromatographic system, and System suitability: Proceed as directed in the Assay. 

Standard solution: 1.5 µg/mL of USP Benzothiadiazine Related Compound A RS in Mobile phase. [Note—A volume of acetonitrile not exceeding 10% of the total volume of the solution may be used to dissolve the USP Reference Standard.] 

Analysis 

Samples: Sample solution and Standard solution 

Calculate the percentage of benzothiadiazine related compound A in the portion of Tablets taken: 

Result = (r_U/r_S) × (C_S/C_U) × 100 

r_U = peak response from the Sample solution  

r_S = peak response from the Standard solution 

C_S = concentration of USP Benzothiadiazine Related Compound A RS in the Standard solution (μg/mL)

C_U = nominal concentration of hydrochlorothiazide in the Sample solution (µg/mL) 

Acceptance criteria: NMT 1.0% 

5 ADDITIONAL REQUIREMENTS 

Packaging and Storage: Preserve in well-closed containers. 

USP Reference Standards 〈11〉 

USP Benzothiadiazine Related Compound A RS 

4-Amino-6-chloro-1,3-benzenedisulfonamide. 

C6H₈ClN₃O₄S₂      285.73 

USP Hydrochlorothiazide RS